The terms “obesity” and “overweight” or “pre-obese” define ranges of weights that are greater than weights that are generally considered to be healthy for a person of a given height. According to a report in August 2010 by the Centers for Disease Control (CDC), “no state met the Healthy people 2010 obesity target of 15%, and the self-reported prevalence of obesity among U.S. adults had increased 1.1 percentage points from 2007” (Sherry et al., Morbidity and Mortality Weekly Report (MMWR), 59; 1-5; Aug. 3, 2010). In children and teens, excess weight represents a very serious health issue. The 2007-2008 National Health and Nutrition Examination Survey (NHANES) estimated that 17% of individuals age 2-19 are obese (CDC). Indeed, the CDC and the WHO have referred to an “obesity epidemic” in many populations worldwide. Overweight and obese individuals have a higher likelihood of developing a variety of health problems including, but not limited to, cardiovascular diseases and associated conditions (e.g., high blood pressure, high cholesterol), type 2 diabetes, respiratory disorders, cancer, reproductive disorders, hepatic dysfunction, and osteoarthritis.
Several different factors can contribute to obesity or being overweight, and the condition can be a complex health issue for many individuals. Behavioral factors, environmental factors, genetics, illness, and/or infectious agents may play a role in the condition. Lack of sufficient physical activity and excess calorie intake in the diet, i.e., caloric imbalance, are the most apparent and common causes of being overweight or obese. However, there appear to be several genetic factors that may predispose certain individuals to weight gain, including mutations in genes related to control of feeding behavior, and various genetic mutations or correlations of genotype with obesity in individuals and populations. In addition to these factors, various illnesses and drugs can also impact an individual's weight. More recently, infectious agents have been identified as contributing to some cases of obesity.
A few infectious agents have been associated with obesity in non-human animals, and one in particular has been associated with human obesity. Human adenovirus-36 (also denoted Ad-36, Adv-36, or hAdv-36) was first described in a child with diabetes in 1980 (Wigand et al., 1980, Arch. Viol. 64(3):225-233). Beginning in the early 1990's, experiments by Dhurandhar and colleagues first showed that Ad-36 increased adiposity in chickens and in mice ((Dhurandhar et al., 1990, J. Bombay Vet. College 2:131-132; Dhurandhar et al., 1992, Vet. Microbiol., 31:101-107; Dhurandhar et al., 2000, Int J Obes Relat Metab Disord 24:989-996; Dhurandar et al., 2001, Int. J. Obes. Relat. Metab. Disord. 25(7):990-996), as well as in monkeys (Dhurandhar, et al., 2002, J. Nutr. 132(10):3155-3160). In mice and chickens, infection with Ad-36 resulted in viremia, infection of adipose tissue, increased visceral fat, total body fat, and/or body weight, and reduced serum cholesterol and triglycerides. In monkeys, Ad-36 promoted weight gain and lowered serum cholesterol. Pasarica and colleagues have shown that human Ad-36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats (Pasarica et al., 2006, Obesity 14(11):1905-1913).
In humans, Ad-36 has been shown to have a high probability of being associated with obesity, where a unique phenotype of low serum cholesterol and triglyceride levels was present in about 30% of obese humans subjects having anti-Ad-36 antibodies, whereas only 5% of the non-obese humans tested had antibodies to Ad-36 (Dhurandhar et al., 1997, FASEB J, 3:A230; Atkinson et al., 1998, Int J Obes Relat Metab Disord 22(Suppl): S57). An epidemiological study showed that 30% of obese people were infected with Ad-36 compared to only 11% of lean people in the study (Atkinson et al., 2005, Int J Obes (Lond), 29(3):281-286). These investigators showed that Ad-36 is associated with increased body weight and the reduction of serum lipids in humans. Additional researchers have reported an association between human Ad-36 and lipid disorders or obesity rates in children and adolescents worldwide (Na et al., 2010, Int. J. Obes. 34:89-93; Gabbert et al., 2010, Pediatrics 2010; 126:721-726; and Atkinson et al., 2010, Int. J. Ped. Obes. 5:157-160). Further work by Pasarica and Dhurandhar and colleagues showed that Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells (Pasarica et al., 2008, Stem Cells 26:969-978). Moreover, in vitro adipogenesis was shown to be accelerated by infection of preadipocytes with human Ad-36 (Vangipuram et al., 2004, Obes. Res. 12(5):770-777), and infection was also shown to increase insulin sensitivity and suppress the expression of leptin mRNA (Vangipuram et al., 2007, Int. J. Obes. (Lond.) 31(1):87-96. The activity of the E4 orf1 gene of Ad-36 has been suggested to be responsible for this adipogenesis (Rogers et al., 2008, International Journal of Obesity 32:397-406).
In 2010, Arnold and colleagues reported the complete characterization of the human Ad-36 genome (Arnold et al., 2010, Virus Res. 149:152-161). Diagnostic assays have been described for the identification of Ad-36 infection in human tissues, via identification or use of anti-Ad-36 antibodies (see, e.g., WO 98/44946, WO 2007/120362), and a diagnostic test for Ad-36 is in commercial development (Scandivir AB). However, a treatment for the viral infection, once identified, is lacking; no preventative or therapeutic treatment that directly targets Ad-36 infection is currently commercially available. Accordingly, there remains a need in the art for an effective prophylactic and/or therapeutic treatment for adenovirus-36 infection, in order to reduce or eliminate Ad-36-associated obesity and overweight conditions.